Schiff bases (SBs) and organophosphonates (OPs) are recognized for their extensive pharmaceutical applications; however, examples of compounds containing both functionalities are rarely reported. This study focuses on synthesizing novel phosphonate Schiff bases (PSBs) by condensing 3-amino benzoic acid with various aldehydes, followed by phosphorylation using triethylphosphite. This synthetic strategy and oxalyl chloride modification of the carboxyl group enabled incorporation of the phosphonate moiety without the need for NH₂ blocking agents, under mild, catalyst-free conditions. Twelve PSBs were synthesized and characterized using ¹H, ¹³C NMR, and HRMS. The compounds exhibited good to excellent yields. Biological evaluations showed significant cytotoxicity and α-glucosidase inhibitory activity. Specifically, compounds P1, P6, P8, and P9 demonstrated potent inhibition with IC₅₀ values of 9.40 ± 0.27, 6.88 ± 0.15, 5.20 ± 0.13, and 10.52 ± 0.26 µM, respectively. These results suggest that PSBs could be promising candidates for treating oncological and diabetic conditions. Advance in vivo studies and clinical trials are required to further establish their pharmacotherapeutic potential.
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